For the diagnosis and prophylaxis of diabetes mellitus, the importance of periodic monitoring of blood glucose levels has been increasingly emphasized. Nowadays, strip-type biosensors designed for hand-held reading devices allow individuals to readily monitor glucose levels in the blood.
A large number of commercialized biosensors measure blood glucose present in blood samples using an electrochemical technique. The principle of the electrochemical technique is based on the following Reaction 1.Glucose+GOx−FAD→gluconic acid+GOx−FADH2 GOx−FADH2+Mox→GOx−FAD+Mred  [Reaction 1]
wherein GOx represents glucose oxidase; GOx−FAD and GOx−FADH2 respectively represent an oxidized and a reduced state of glucose-associated FAD (flavin adenine dinucleotide), a cofactor required for the catalyst of glucose oxidase; and Mox and Mred denote an oxidized and a reduced state, respectively, of an electron transfer mediator.
The electrochemical biosensor uses as electron transfer mediators organic electron transfer materials, such as ferrocenes or their derivatives, quinines or their derivatives, organic or inorganic materials containing transition metals (hexamine ruthenium, polymer containing osmium, potassium ferricyanide and the like), organic conducting salts, and viologens.
The principle by which blood glucose is measured using the biosensor is as follows.
Glucose in the blood is oxidized to gluconic acid by the catalysis of glucose oxidase, with the cofactor FAD reduced to FADH2. Then, the reduced cofactor FADH2 transfers electrons to the mediator, so that FADH2 returns to its oxidized state; that is, FAD and the mediator are reduced. The reduced mediator is diffused to the surface of the electrodes. The series of reaction cycles is driven by the anodic potential applied at the working electrode, and the redox current proportional to the level of glucose is measured. Over biosensors based on colorimetry, the electrochemical biosensors (that is, based on electrochemistry) have the advantages of not being influenced by the turbidity or color of the samples and allowing the use of wider range of samples, even cloudy ones, without pretreatment thereof.
Although this electrochemical biosensor is generally conveniently used to monitor and control the amount of blood glucose, its accuracy is greatly dependent on deviations according to each mass-production lot in which the biosensors are produced. In order to eliminate this deviation, most commercialized biosensors are designed such that a user directly inputs calibration curve information, which is predetermined at the factory, into a measuring device capable of reading the biosensor. However, this method is highly inconvenient for the user and causes the user to make input errors, thus leading to inaccurate results.
In order to solve such problems, a method by which the resistance of each electrode can be adjusted such that the variations in mass production is corrected (US20060144704A1), a method in which a conductor is printed in a bar code fashion on the biosensor strip to record the production information (U.S. Pat. No. 6,814,844), a method in which a connection to a resistor bank is made (WO2007011569A2), and a method by which information is read by varying resistance through the adjustment of the length or thickness of each electrode (US20050279647A1) have been proposed. The methods proposed for the electrochemical biosensors are all based on a technique with which electrical variation can be read. Furthermore, a method for distinguishing production lot information by reading the resistivity of a conductor marked on a strip using an electrical method (U.S. Pat. No. 4,714,874) has been proposed.
However, these methods serve to accurately adjust resistance, and require a process of mass-producing the sensors first, measuring the statistical characteristics of the sensors, and post-processing the measured information again using a method of adjusting the resistance marked on the sensors. However, the process of accurately adjusting the resistance, marked in large quantities, through the post-processing is very inconvenient, and is difficult to use for practical application.
Methods in which colored marks are used to enable a spectral system capable of discriminating colors to use a colorimetric method (U.S. Pat. Nos. 3,907,503, 5,597,532, 6,168,957), a method in which a plurality of color marks is read at various wavelengths of visible and infrared ray regions using a spectroscope (U.S. Pat. No. 5,945,341), and a method in which bar codes are read (EP00075223B1, WO02088739A1) have been proposed. These methods, using color or bar codes, are favorable for a colorimetric method-based sensor using the spectrum system, but they have technical and economic difficulties when applied to systems using an electrochemical measurement mechanism. For example, the size and structure of the portion where the electrochemical sensor strip is inserted into the measuring device for the purpose of electrical connection, that is, the connection space of the sensor strip, is very limited when constructing a device and circuit for spectroscopically identifying the structure into which the production lot information is input. Further, color discrimination requires a process of scattering and identifying various wavelengths of light detected using a detector and a complicated process, that is, the conversion of analog signals into digital signals and the calculation thereof, with the concomitant accompaniment of a device and its program therefor. Thus, the expenses incurred when constructing the system are greatly increased.
Furthermore, instead of the methods of marking the production lot information on the sensor strip, a method of recording information on a container or pack containing a sensor and allowing the information to be read by the measuring device (EP0880407B1) has been proposed. However, this method also has a possibility of causing the user to make an error of incorrectly reading a code recorded on the container.
Leading to the present invention, intensive and thorough research into electrochemical biosensors, conducted by the present inventors, aiming to maintain economic efficiency in the construction of the measuring device while allowing the mass production of the electrochemical biosensor, which allows the production lot information thereof to be easily and accurately input into the measuring device without mistakes on the part of the user, and thus provides an accurate measurement value, resulted in the finding that, when the production lot information is recorded in the form of magnetization marks on the electrochemical biosensor strip and read in the measuring device, a micro magnetoresistance sensor device can be employed to detect the magnetization marks, without the need for a high-priced magnetic reader, so that the magnetic detector system has a simple construction and thus can not only reduce a complicated calculation process, performed for post-treatment, but also maintain economic efficiency in the construction of the measuring device.